Outcome of nucleos(t)ide analog intervention in patients with preventive or on‐demand therapy for hepatitis B virus reactivation

Abstract

Preventive or on‐demand nucleos(t)ide analog (NA) therapy can prevent severe hepatitis related to hepatitis B virus reactivation (HBV‐R). However, it is unclear if NA can be safely stopped in such patients after cytotoxic therapies or during immunosuppressive therapies. We retrospectively evaluated 133 patients who initiated NA therapy between 2007 and 2018. A total of 103 patients were positive for HBV surface antigen (HBsAg) at baseline, and NA therapy was started before cytotoxic or immunosuppressive therapy (preventive group). Thirty patients with resolved HBV infection were treated with NA therapy after HBV reactivation (on‐demand group). Virological relapse was defined as a serum HBV DNA level >20 IU/ml. NA therapy was stopped in 12 (12%) patients (preventive group), and in 16 (53%) patients (on‐demand group). After the cessation of NA therapy, the cumulative rates of relapse were 36% and 39% at 12 and 24 months, respectively. High levels of HBsAg both at baseline and at the cessation of NA therapy were related to the occurrence of relapse. Relapse did not occur in patients with HBsAg levels <20 IU/ml (preventive group). HBV relapse occurred in five (33%) patients in the on‐demand group. Relapse occurred only in anti‐HBs‐negative patients at the cessation of NA therapy. There were no cases of hepatitis flare after the cessation of NA therapy. HBsAg predicted HBV relapse after the cessation of NA therapy in HBsAg‐positive patients. Anti‐HBs could be a predictive marker for NA therapy cessation in patients with resolved HBV.

Management of hepatitis B virus (HBV) reactivation in patients with resolved HBV infection based on a highly sensitive HB core‐related antigen assay

“…In comparison, this newly developed, fully automated, highly sensitive iTACT‐HBcrAg assay could predict not only the risk of progression to hepatocellular carcinoma in patients with chronic HBV infection, but also monitor HBeAg‐negative patients who have low levels of HBV DNA with or without NA treatment 21,22 . Recently, iTACT‐HBcrAg was reported to be a useful potential serological marker to diagnosing early‐stage HBV reactivation in patients with resolved HBV infection 10 . Some guidelines recommend that HBV DNA monitoring‐guided preemptive antiviral therapy is an effective strategy to prevent de novo hepatitis due to HBV reactivation in patients with resolved HBV infection, especially in those who received anti‐CD20 antibody‐containing chemotherapy 20–22 .…”

“…Little evidence exists regarding the optimal duration of NA treatment and the risk of recurrence of HBV reactivation after the cessation of NA in patients with resolved HBV infection. Recently, a retrospective observational study showed that recurrence of HBV reactivation was observed in 6 (38%) of 16 patients with resolved HBV infection who received and then discontinued NA treatment 10 . Interestingly, that study showed that no recurrence of HBV reactivation was observed in 10 patients with anti‐HBs titers of 10 mIU/ml or more at the cessation of NA treatment 10 .…”

“…Regular HBV DNA monitoring‐guided preemptive antiviral therapy using anti‐HBV nucleos(t)ide analogs (NA) can completely prevent HBV‐related hepatitis in patients with resolved HBV infection following anti‐CD20 antibody‐containing systemic chemotherapy 7–9 . However, little evidence exists regarding such NA treatment after HBV reactivation in patients with resolved HBV infection, including the cessation criteria of NA 10 …”

Tenofovir alafenamide for prevention and treatment of hepatitis B virus reactivation and de novo hepatitis

“…Several NA studies have shown that prophylaxis with entecavir (ETV) and TDF was significantly associated with a lower risk of HBV reactivation 19–23 . However, there are no studies evaluating the efficacy of TAF as prophylaxis against or treatment for HBV reactivation.…”

“…Several NA studies have shown that prophylaxis with entecavir (ETV) and TDF was significantly associated with a lower risk of HBV reactivation. 19 , 20 , 21 , 22 , 23 However, there are no studies evaluating the efficacy of TAF as prophylaxis against or treatment for HBV reactivation. It is necessary that a study be conducted to compare the efficacy and safety between ETV and TAF as prophylaxis against or treatment for HBV reactivation.…”